PROJECT SUMMARY Age is the largest single risk factor for the majority of diseases seen in clinics throughout the U.S. Demo- graphic calculations predict that eliminating any single age-related disease would produce only a modest in- crease in human health span (years of healthy life) or life span. However, postponing or decreasing the rate of aging would retard the course of multiple age-related diseases and thus substantially increase health span and likely life span. Our ability to develop rational approaches to preventing or intervening in the debilitating and costly consequences of aging depends crucially on a thorough understanding of the causes of aging and how they interact with the etiology of specific age-related diseases. Training young scientists to integrate research on basic aging mechanisms with mechanisms of specific age-related diseases is a critical objective of this ap- plication. The long-term goal of this training program is to provide exceptional young scientists with the broad knowledge, skills and interactions they will need to mitigate, through research, the enormous human and finan- cial burdens caused by aging and age-related diseases. This program will train postdoctoral fellows to become future leaders in aging research. Each year, the program will train 10 talented postdoctoral scientists who will conduct research for a 2-year period in one or more of 36 laboratories headed by outstanding preceptors at the Buck Institute for Research on Aging, Lawrence Berkeley National Laboratory, University of California, Berke- ley and Stanford University. Trainees will participate in research projects that include basic mechanisms of cellular stress responses, protein homeostasis, genomic and epigenomic stability, stem cell maintenance, bio- energetics and energy metabolism and hormonal, growth factor and nutrient signaling pathways. They will uti- lize a variety of model systems including yeast, round and flat worms, fruit flies, fish, mice and human cells and tissues. And they will focus on an array of age-related diseases including Alzheimer's, Parkinson's and Hun- tington's diseases, stroke, cardiac and vascular dysfunction, cancer, diabetes, osteoporosis and sarcopenia. Trainees will be instructed in state-of-the-art techniques in genomics, epigenomics, drug screening, proteomics and metabolomics, as well as genetics, biochemistry, structural biology, cell biology, and cell and organismal imaging. They will receive the benefits of diverse seminar series and other scientific events and frequent net- working opportunities. They will also attend courses in specialized scientific topics, as well as courses or dis- cussion groups on geriatric medicine, ethics, presentation skills, proposal and manuscript writing, and laborato- ry management skills. The program will fill an important national and international need for high-quality ad- vanced training that integrates basic aging research with research on age-related disease.